1. Field of the Invention
Medical imaging with X-rays depends to a great extent upon radiographic contrast media (CM). An ideal CM, designed to mix with the body fluids, should be economically feasible, chemically stable, high water soluble, readily injectable, and biologically inert. CM of prior art, based on salts of derivatized triiodinated benzene moieties and meet the first four criteria, but they induce adverse clinical effects. Such toxicity extends from their ionicity, solution hyperosmolality vis-a-vis the body fluids, and chemotoxicity reflecting their relatively high hydrophobicity.
Non-ionic, less hyperosmolal, less hydrophobic but more costly compounds exist, of which Metrizamide is used clinically in the United States. Metrizamide suffers from hydrolytic instability, and thus must be dispensed lyophilized and reconstituted prior to use. Solutions of some other non-ionic, stable CM have, however, high osmolality and thus elicit pain when injected into the arteries. Other compounds are, at elevated concentrations, not persistently water soluble. All current non-ionic CM, while less toxic than the prior art, are much more costly.
Consequently despite the large number of compound which have been prepared, there is substantial interest in producing improved non-ionic CM improved both pharmacologically and economically. To this end, in developing novel synthetic strategies, it is essential once the ring has been iodinated that subsequent steps are few and have high yields. Furthermore, the iodinated substrate, as well as the reactants that are employed for additional functionalization, should be inexpensive.